This invention relates to a novel method for heat-sterilizing artificial kidneys, and to artificial kidneys suitable for use in heat sterilization by this method.
An artificial kidney is already known which includes a receptacle having accommodated therein permselective hollow flaments and comprising blood inlet and outlet ports and dialyzate inlet and outlet ports. The artificial kidney performs the function of kidneys of the living body by the removal of wastes from the blood into the dialyzate and the ultrafiltration of excess water in the blood. The importance of hollow filaments-containing artificial kidneys has increased rapidly because of their small sizes for the available membrane area and their ease of use.
It is necessary to sterilize artificial kidneys during production so as to avoid microbial contamination, and to supply them in the microbe-free state to the users. The users perform a necessary pretreatment on the sterilized artificial kidneys prior to use.
In the past, pre-use sterilization of artificial kidneys has been performed mainly by the following two typical methods.
According to one method, the manufacturers sterilize the artificial kidneys by filling them with an aqueous solution of formaldehyde which is relatively concentrated, and usually has a concentration of 1 to 5%, and ship them in the sterilized state. Prior to use for dialysis, the users remove the formaldehyde by washing, warm the artificial kidneys to the body temperature, and perform other necessary treatments (for example, fill a physiological saline solution containing heparin into the blood-flowing section of the artificial kidneys). This method permits effective sterilization. However, since the formaldehyde used as a sterilizing agent is toxic to man, it must be completely removed from the artificial kidneys. This requires the flowing of a great quantity of water for a long period of time. Such a washing operation is troublesome, and the users must spend considerable labor and time. There is an additional defect that if washing is stopped after the formaldehyde concentration in the washing effluent has decreased and no substantial formaldehyde is detected, the formaldehyde remaining in the hollow filaments gradually oozes out of the filaments.
According to the other method, the manufacturers sterilize the artificial kidneys by passing a gaseous mixture, consisting of 10 to 30% ethylene oxide or propylene oxide as a sterilizing ingredient and the remainder being Freon.RTM. or CO.sub.2 as a carrier ingredient, into the artificial kidneys in the dried state, and ship them in the sterilized condition. Prior to use, the users perform necessary treatments on the dried sterilized artificial kidneys; for example, they fill them with a dialyzate and an isotonic saline solution. This method has the defect that gases such as ethylene oxide or propylene oxide are adsorbed by the hollow filaments, and the gases remaining in the filaments react with chlorine ions in the physiological saline solution to form a toxic chlorohydrin compound. Washing of these residual gases require the passing of a physiological saline solution in an amount of as large as more than 2 liters. Furthermore, since the hollow filaments of the artificial kidneys are capillary tubes, in order to remove the bubbles completely, the washing liquid must be passed for longer periods of time, or the washing liquid must be passed after replacing the air in the hollow filaments by aseptic carbon dioxide gas. In the latter case, the users require various devices such as a carbon dioxide gas cylinder, a sterilizing filter, a pressure control device, or a flow rate controlling device. If the bubbles remain in the hollow filaments, minute bubbles are very likely to flow into the body during dialysis, or may cause coagulation of the blood within the hollow filaments, thus increasing the amount of the blood remaining in the dialyzer afer dialysis, and also losses of the blood.
Furthermore, since by the gas sterilizing method, artificial kidneys in the dried state are rendered wet by pretreatment, the performance of the artificial kidneys tends to change, and has poor reproducibility.
A third sterilizing method suggested involves applying gamma-rays in a dose of 0.5 to 5 Mrads to artificial kidneys. This radiation sterilizing method is free from a problem of residual toxicity, but, as in the second method, tends to cause changes in the performance of the artificial kidneys in pretreatments, such as the filling of a physiological saline solution and a dialyzate into the artificial kidneys in the dried state. In addition, the materials which constitute the artificial kidneys are susceptible to degradation by application of ionizing radiation, and problems are still left unsolved in the improvement and choice of materials.
Generally, sterilization also includes heat sterilization which is widely practised for the sterilization of injection syringes and instruments for surgical operation. For example, Japanese Pharmacopoeia, the 9th revised edition, sets forth a method for controlling microorganisms by a high-pressure steam sterilizing method which comprises heating the material to be sterilized in saturated steam at 115.degree. C. for 30 minutes, at 121.degree. C. for 20 minutes, or at 126.degree. C. for 15 minutes. The Japanese Pharmacopoeia also permits the use of an intermittent sterilizing method which comprises heating the material to be sterilized for 30 to 60 minutes in water or flowing steam at 80.degree. to 100.degree. C. every 24 hours, and repeating this heating operation 3 to 5 times.
Since heat sterilization is advantageous because of the freedom from residual toxicity and the ease of washing, it would be very convenient if this method can be applied to artificial kidneys. In fact, the heat sterilizing method has never been applied to artificial kidneys, and no attempt at it has been made because it has been considered as quite impossible to heat sterilize artificial kidneys filled with a primer. The reason for this is that upon heating, the artificial kidneys undergo deformation, cracking or breakage owing to the thermal expansion of the primer and the air contained in the artificial kidneys and the generation of the autogenous pressure of steam, and consequently, leakage of the primer occurs, and also, it is difficult to seal artificial kidneys aseptically after sterilization.
The present invention has successfully solved the above problems.
It is an object of this invention to provide a method for heat sterilizing artificial kidneys filled with a primer.
Another object of this invention is to supply to the users artificial kidneys which do not substantially require pretreatment.